Sotagliflozin Makes Waves at AHA 2020 with Phase 3 SOLOIST and SCORED

Deepak Bhatt, MD, MPH

A novel diabetes medication is making waves thanks to a pair of late-breaking studies presented at the American Heart Association’s Scientific Sessions 2020.

Data from the phase 3 SOLOIST-WHF and SCORED trials suggest sotagliflozin was associated with significant reductions in death from cardiovascular disease in patients with worsening heart failure and significant reductions in blood glucose levels among patients with moderate to severe kidney impairment.

"With the results of these large two trials, adding to other recent data about drugs in this class, it is now clear that most patients with type 2 diabetes and either kidney disease or heart failure should be on an SGLT2 inhibitor," said Deepak Bhatt, MD, MPH, the executive director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital, in a statement. "SCORED provides further randomized clinical trial evidence that SGLT2 inhibitors should be part of the standard of care for patients with type 2 diabetes mellitus and kidney disease. And SOLOIST demonstrates that early, in-hospital initiation of SGLT2 inhibitors is safe, effective, and should become the standard of care in patients with type 2 diabetes mellitus and heart failure."

Developed by Sanofi Inc. and transferred to Lexicon Pharmaceuticals, sotagliflozin is the first dual SGLT2/1 inhibitor being developed for the treatment of type 1 and type 2 diabetes. With the recent increase in interest related to the cardiorenal protection seen with SGLT2 inhibitors, investigators sought to explore use of sotagliflozin in specific diabetic populations.

SOLOIST-WHF was designed as a multicenter, double-blind trial of patients with type 2 diabetes who were recently hospitalized for worsening heart failure. The trial randomized 1222 patients in a 1:1 ratio to sotagliflozin or placebo. The primary endpoint of the trial was the total number of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure. Of the 608 patients in the sotagliflozin group, 48.8% received the first dosage before discharge and the remaining 51.2% received the first dose a median of 2 days after discharge.

Of note, SOLOIST-WHF was ended early due to a lack of funding from the sponsor during the COVID-19 pandemic and the median follow-up time was 9.0 months.

SCORED was similar in design, but enrolled patients with type 2 diabetes, chronic kidney disease, and risks for cardiovascular disease. This trial enrolled 10,584 patients in a 1:1 ratio and patients were followed for a median of 16 months. The primary endpoint of the trial was a composite of the total number of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure. SCORED was also ended early due to a lack of funding during the pandemic.

Results of SOLOIST-WHF suggested sotagliflozin was associated with fewer primary endpoint events (245 vs 355) compared to placebo and a lower rate of primary endpoint events (51.0 vs. 76.3; HR, 0.67; 95% CI, 0.52-0.85; P <.001) compared to placebo. Results from this trial also suggested sotagliflozin was associated with a lower rate of death from cardiovascular causes (HR, 0.84; 95% CI, 0.58-1.22) and rate of all-cause mortality (HR, 0.82; 95% CI, 0.59-1.14). Additionally, investigators found these results were consistent regardless of when first dose was administered.

Results of SCORED indicated sotagliflozin was associated with a lower rate of primary endpoint events HR, (0.74; 95% CI, 0.63-0.88; P <.001) anda lower rate of deaths from cardiovascular causes (HR, 0.90; 95% CI, 0.73-1.12; P=.35). Results also suggested sotagliflozin was associated with a reduction in first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke (HR, 0.84; 95% CI, 0.72-0.99) and the first occurrence of death from cardiovascular causes or hospitalization for heart failure, which were the original coprimary endpoints of the trial.

"Sotagliflozin is the first SGLT2 inhibitor to show a beneficial effect on stroke among patients with diabetes, suggesting that it may also affect atherosclerosis, or plaque build-up in the coronary and brain arteries,” added Bhatt. “SCORED is also the first trial to show the benefits of SGLT2 inhibitors across the full range of albuminuria, or leakage of protein in the urine, which is common in people with Type 2 diabetes.”

These studies, “The Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure (SOLOIST-WHF),” and “Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk (SCORED),” were presented at AHA 2020 and simultaneously published in The New England Journal of Medicine.